This invention relates to a process for preparing intermediates useful in the preparation of prostaglandins (hereinafter identified as "PGF.sub.2.sub..alpha. ", "PGF.sub.2.sub..alpha. ", etc.), to certain novel intermediates, and to processes for resolving the optical isomers of those intermediates.
Previously, a racemic bicyclic lactone diol of the formula ##SPC2##
Was reported by E. J. Corey et al., J. Am. Chem. Soc. 91, 5675 (1969), and later disclosed in an optically active form by E. J. Corey et al., J. Am. Chem. Soc. 92, 397 (1970). Conversion of this intermediate to PGE.sub.2 and PGF.sub.2.sub..alpha., either in dl-form or optically active form, was disclosed in those publications.
Similarly, an optically active compound of the formula ##SPC3##
Wherein THP is tetrahydropyranyl, and its conversion to PGE.sub.3 and PGF.sub.3.sub..alpha. was reported by E. J. Corey et al., J. Am. Chem. Soc. 93, 1490 (1971).
Subsequent to this invention, the compound ##SPC4##
Wherein THP is tetrahydropyranyl and the process for making same were reported by E. J. Corey et al., J. Am. Chem. Soc. 94, 4014 (1972).
The known prostaglandins include, for example, prostaglandin E.sub.2 (PGE.sub.2), prostaglandin F.sub.2 alpha and beta (PGF.sub.2.sub..alpha. and PGF.sub.2.sub..beta.), prostaglandin A.sub.2 (PGA.sub.2), prostaglandin B.sub.2 (PGB.sub.2), and the corresponding PG.sub.3 compounds. Each of the above-mentioned known prostaglandins is a derivative of prostanoic acid which has the following structure and atom numbering: ##SPC5##
See, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. A systematic name for prostanoic acid is 7-[(2.beta.-octyl)-cyclopent-1.alpha.-yl] -heptanoic acid.
PGE.sub.2 has the following structure: ##SPC6##
PGF.sub.2.sub..alpha. has the following structure: ##SPC7##
Pge.sub.3 has the following structure: ##SPC8##
Pgf.sub.3.sub..alpha. has the following structure: ##SPC9##
The prostaglandin formulas mentioned above each have several centers of asymmetry. Each formula represents a molecule of the particular optically active form of the prostaglandin obtained from certain mammalian tissues, for example, sheep vesicular glands, swine lung, and human seminal plasma, or by reduction or dehydration of a prostaglandin so obtained. See, for example, Bergstrom et al., cited above, and references cited therein. The mirror image of each formula represents a molecule of the other enantiomeric form of that prostaglandin. The racemic form of the prostaglandin consists of equal numbers of two types of molecules, one represented by one of the above formulas and the other represented by the mirror image of that formula. Thus, both formulas are needed to define a racemic prostaglandin. See Nature 212, 38 (1966) for discussion of the stereochemistry of the prostaglandins.
In the formulas above, as well as in the formulas given hereinafter, broken line attachments to the cyclopentane ring indicate substituents in alpha configuration, i.e., below the plane of the cyclopentane ring. Heavy solid line attachments to the cyclopentane ring indicate substituents in beta configuration, i.e., above the plane of the cyclopentane ring. In the formulas above, the hydroxyl attachment to carbon 15 is in the alpha (or S) configuration, as indicated by the broken line. In formulas below, this convention is also used for intermediates having hydroxyl substitution at the corresponding position on the side chain. A wavy line .about. indicates optional attachment in either alpha or beta configuration. Reference to the "S" configuration follows the convention used in the art. See for example Nugteren et al., Nature 212, 38 (1966); Cahn, J. Chem. Ed. 41, 116 (1964): and "Basic Principles of Organic Chemistry", J. D. Roberts and M. C. Casero, W. A. Benjamin, Inc., N.Y., 1964, pp. 592-594.